Breast cancer - Hope or reality?
Kat - At a somewhat gladatorial debate hosted by the charity Breakthrough Breast Cancer on the first night of the NCRI Cancer Conference, researchers debated whether treating metastatic breast cancer - that's breast cancer that has spread through the body - with genetically targeted therapies is hype or reality. To get a flavour of the discussion, I talked to two of the expert speakers - Dr David Miles from Mount Vernon Cancer Centre, and first, Professor David Cameron (no relation to the one at Number 10) from the University of Edinburgh.
David C. - I think one of the key points is, it's not just the future. It is also happening today and the biggest and best example is, when we use treatments to target to the HER2 oncogene. But this is gene which are multiple copies in some breast cancers that alters the behaviour of the cancer and allows us to target it therapeutically.
Kat - And that's with the drug Herceptin that people have heard of.
David C. - So, this is something that we can already use to treat some of our breast cancer patients.
Kat - And this is all stuff that's come from our understanding of the genetic faults, the molecular nuts and bolts of what's gone wrong in cancer cells.
David C. - Exactly. Now it's true, we haven't got a map that allows us to target every single observed or measured genetic change, but the reality is, we're able to do it for some people now. By mapping that in more detail, I believe that there'll be more patients inn whom this will become a reality.
Kat - And you David, you're a little bit more sceptical about this being the way forwards. Tell me where you're coming from.
David M. - Like many developments in their infancy, this is being somewhat overhyped. So, there is the suggestion that by understanding the alterations in the genome, that that will necessarily result in treatments that can target those alterations. Now, in some tumours, that may be true. In breast cancer, we're still struggling to understand what the driver mutations are. Now, the HIR2 alteration in breast cancers, that was not really discovered through changes in genomics. That was through understanding signal transduction. Now of course, it does eventually go back to genomics, but that advance in treatment of patients with that sort of breast cancer wasn't made through genomics.
So, I think my argument is that just because you can take a picture of a very, very complex situation does not automatically mean that you're going to have useable treatments. Such is the complexity of the biology that just squeezing one particular pathway, you're going to have compensatory mechanisms many, many times, meaning that that therapy is very rapidly overcome and bypassed. So, I think it is very much work in progress. Now, I'm not convinced in breast cancer metastatic disease at least that it is actually reality now in those terms of using the genome to develop targetable lesions.
Kat - One of the things that we've heard a lot about lately is this concept of tumour heterogeneity - not all the cells in a cancer being the same- and also, tumours evolving within the body, becoming resistant to treatments, as you say. Is this as you see it, the biggest block to using this kind of targeted treatments?
David M. - Yeah. I mean, in my arguments with David here, I was sort of trying to use that Darwinian principle that says, "If put pressures on an organism or a cancer cell from one side or another, it will develop changes and adapt to overcome those particular pressures" and I think that's what the challenge is going to be. So, cancer is extremely smart and we are relatively dumb.
Kat - David Cameron, cancer is smart and we are dumb. How do we go forward from here?
David C. - I hate to agree with an opponent in the debate but I think you make a very valid point. We've been rather dumb about this. I think there's been a very naïve expectation that by spotting a few mutations we will suddenly have a few wonder drugs. The argument here I think is that we need to be clever and think in a more complex way and realise that what drives a cancer's behaviour are the genetic changes. And they're very good at acquiring new ones. Have we sat and worked out which are the key drivers that allow that mutational picture to appear? If we simply pick off a few mutations because we happen to be able to and that some of the hype has been expected from outside, that's probably where we go wrong.
But that hard reality is, that's what's happening in the cancers in the patients. It is a genomic mess and I think we've been simplistic in how we've approached. We need to be smarter. We will never be as smart as a cancer, but if we could understand better the complexity of that genome picture - the challenge of drugging what's called the undruggable, and some of these may look in our current science as undruggable, we've cracked it before and I'm sure we'll crack some of them again.
David M. - It is comparatively easy to look at the genome level. It is much, much more difficult to look at the protein level. I think we have to look at all aspects of expression really to understand the pathways. So, we have to look at all aspects of how the cancer cell behaves.
Kat - There's lots of researchers around the world that are doing things like the International Cancer Genome Consortium, sequencing the DNA and mutations of lots and lots of tumours. So, do we just have to wait until our technology catches up to look in this greater detail?
David M. - I think it's not so much the technology. I think what is clear is that ascertaining the genome is becoming very, very straightforward. I think the informatics that is the biggest, biggest challenge.
David C. - And mixing that as you said with more than just a straight genetic mutational picture. How do we do that? We can't ignore any one of them.
Kat - To sort of wrap up, one point that was raised was that a hundred years ago, we would've looked at breast cancer patients today and said, "We can hardly cure any of them" and today, women with breast cancer will survive for several decades. Do you think maybe painting a picture, 50 years in the future that this will be a debate that - we have this debate now but actually, then we discovered that we could cure these women, thanks to genomic medicine. What's your hope?
David C. - I think we will cure more of them. It will be lovely to predict that we'll cure them all, but the reality is, I think at the moment, cancer is telling us, well, you're chipping away at me, but ultimately sadly, they'll still win for some patients. But yes, I believe with genomics and working in a multivariable way with the other -omics, we will cure more of them.
Kat - David Miles.
David M. - I think it will have a place ultimately. I think the point we were trying to make this evening is the fact that a patient coming in through the clinic today has an expectation that somehow, by understanding the changes at that DNA level means I can make a difference to their treatment today. Sadly, we are not there. We may be there in some years' time but it's going to be a long haul.
Kat - That was David Miles from Mount Vernon Cancer Centre and also you heard David Cameron from Edinburgh University, discussing whether genomic medicine for breast cancer is hype or reality, after their Breakthrough Breast Cancer-sponsored debate at the NCRI Cancer Conference.